Evidence-Based Reviews

Do stimulants for ADHD increase the risk of substance use disorders?

Current Psychiatry. 2011 August;10(8):20-24

For some patients, stimulants might protect against future SUDs

References

1. Lambert NM, McLeod M, Schenk S. Subjective responses to initial experience with cocaine: an exploration of the incentive-sensitization theory of drug abuse. Addiction. 2006;101(5):713-725.

2. Mannuzza S, Klein RG, Moulton JL. Does stimulant treatment place children at risk for adult substance abuse? A controlled prospective follow-up study. J Child Adolesc Psychopharmacol. 2003;13(3):273-282.

3. Katusic SK, Barbaresi WJ, Colligan RC, et al. Psychostimulant treatment and risk for substance abuse among young adults with a history of attention-deficit/hyperactivity disorder: a population-based, birth cohort study. J Child Adolesc Psychopharmacol. 2005;15(5):764-776.

4. Wilens TE, Faraone SV, Biederman J, et al. Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003;111(1):179-185.

5. Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999;104(2):e20.-

6. Katusic SK, Barbaresi WJ, Colligan RC, et al. Psychostimulant treatment and risk for substance abuse among young adults with a history of attention-deficit/hyperactivity disorder: a population-based, birth cohort study. J Child Adolesc Psychopharmacol. 2005;15(5):764-776.

7. Wilens TE. Impact of ADHD and its treatment on substance abuse in adults. J Clin Psychiatry. 2004;65(suppl 3):38-45.

8. Barkley RA, Fischer M, Smallish L, et al. Young adult follow-up of hyperactive children: antisocial activities and drug use. J Child Psychol Psychiatry. 2004;45(2):195-221.

9. Mannuzza S, Klein RG, Bessler A, et al. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry. 1993;50(7):565-576.

10. Wilens TE. Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship subtypes at risk, and treatment issues. Psychiatr Clin North Am. 2004;27(2):283-301.

11. Wilens TE. AOD use and attention deficit/hyperactivity disorder. Alcohol Health Res World. 1998;22(2):127-130.

12. Wilens TE, Biederman J, Abrantes AM, et al. Clinical characteristics of psychiatrically referred adolescent outpatients with substance use disorder. J Am Acad Child Adolesc Psychiatry. 1997;36(7):941-947.

13. Schubiner H, Tzelepis A, Milberger S, et al. Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance abusers. J Clin Psychiatry. 2000;61(4):244-251.

14. Lambert NM, Hartsough CS. Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil. 1998;31(6):533-544.

15. Zucker RA. Alcohol use and the alcohol use disorders: a developmental biopsychosocial systems formulation covering the life course. In: Cicchetti D Cohen D, eds. Developmental psychopathology. 2nd ed. Hoboken, NJ: John Wiley & Sons Inc; 2006;620-656.

16. Caspi A, Moffitt TE, Newman DL, et al. Behavioral observations at age 3 years predict adult psychiatric disorders. Longitudinal evidence from a birth cohort. Arch Gen Psychiatry. 1996;53(11):1033-1039.

17. Màsse LC, Tremblay RE. Behavior of boys in kindergarten and the onset of substance use during adolescence. Arch Gen Psychiatry. 1997;54(1):62-68.

18. Nigg JT, Wong MM, Martel MM, et al. Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders. J Am Acad Child Adolesc Psychiatry. 2006;45(4):468-475.

19. Seidman LJ, Valera EM, Makris N. Structural brain imaging of attention-deficit hyperactivity disorder. Biol Psychiatry. 2005;57(11):1263-1272.

20. Biederman J, Wilens T, Mick E, et al. Is ADHD a risk factor for psychoactive substance use disorders? Findings from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry. 1997;36(1):21-29.

21. Wilens TE, Biederman J, Millstein RB, et al. Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder. J Am Acad Child Adolesc Psychiatry. 1999;38(6):680-685.

22. Schubiner H, Saules KK, Arfken CL, et al. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Exp Clin Psychopharmacol. 2002;10(3):286-294.

23. Katusic SK, Barbaresi WJ, Colligan RC, et al. Psychostimulant treatment and risk for substance abuse among young adults with a history of attention-deficit/hyperactivity disorder: a population-based, birth cohort study. J Child Adolesc Psychopharmacol. 2005;15(5):764-776.

24. Flory K, Milich R, Lynam DR, et al. Relation between childhood disruptive behavior disorders and substance use and dependence symptoms in young adulthood: individuals with symptoms of attention-deficit/hyperactivity disorder and conduct disorder are uniquely at risk. Psychol Addict Behav. 2003;17(2):151-158.

25. Wilens TE. Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship subtypes at risk, and treatment issues. Psychiatr Clin North Am. 2004;27(2):283-301.

26. Wilson JJ. ADHD and substance use disorders: developmental aspects and the impact of stimulant treatment. Am J Addict. 2007;16(suppl 1):5-11.

27. Lambert NM, Hartsough CS. Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil. 1998;31(6):533-544.

28. Biederman J, Monuteaux MC, Spencer T, et al. Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study. Am J Psychiatry. 2008;165(5):597-603.

29. Wilens TE, Faraone SV, Biederman J, et al. Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003;111(1):179-185.

30. Faraone SV, Wilens TE. Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse abuse, and diversion. J Clin Psychiatry. 2007;68(suppl 11):15-22.

31. Wilens TE, Adamson J, Monuteaux MC, et al. Effect of prior stimulant treatment for attention-deficit/hyperactivity disorder on subsequent risk for cigarette smoking and alcohol and drug use disorders in adolescents. Arch Pediatr Adolesc Med. 2008;162(10):916-921.

32. Barkley RA, Fischer M, Smallish L, et al. Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study. Pediatrics. 2003;111(1):97-109.

33. Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry. 2008;47(1):21-31.

34. Upadhyaya HP, Rose K, Wang W, et al. Attention-deficit/hyperactivity disorder, medication treatment, and substance use patterns among adolescents and young adults. J Child Adolesc Psychopharmacol. 2005;15(5):799-809.

35. Kollins SH. A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders. Curr Med Res Opin. 2008;24(5):1345-1357.

36. Faraone SV, Biederman J, Wilens TE, et al. A naturalistic study of the effects of pharmacotherapy on substance use disorders among ADHD adults. Psychol Med. 2007;37(12):1743-1752.

Discuss this article at www.facebook.com/CurrentPsychiatry

Does prescribing stimulants to patients with attention-deficit/hyperactivity disorder (ADHD) increase their risk of future substance abuse? Because ADHD is a common pediatric condition with symptoms that often persist into adulthood, and stimulants are an efficacious first-line therapy, this possible association is a concern for psychiatrists whether they treat children or adults.

Some researchers have expressed concerns that stimulant exposure could predispose patients to future substance abuse.¹ Proponents of the biologic model of “kindling” hypothesize early exposure to stimulants could increase the risk of later substance use disorders (SUDs) by modifying or “priming” the brain, which then becomes more receptive to illicit drug exposure. Although there is some evidence that stimulant use does increase SUD risk, other evidence suggests stimulant use does not increase susceptibility to SUDs^2,3 and some studies have suggested stimulant use in ADHD patients may protect against SUDs.^4,5

This article reviews shared characteristics of ADHD and SUDs and the latest research on the association between the clinical use of stimulants and later development of SUDs. We also offer clinical recommendations for assessing and treating ADHD and comorbid SUD.

ADHD/SUD overlap

Compared with those without the disorder, patients with ADHD have a 6.2 times higher risk of developing an SUD.⁶ Individuals with ADHD experience an earlier age of onset and a longer duration of SUDs.⁷ Several retrospective and prospective studies reveal ADHD is a risk factor for SUDs.⁸ A longitudinal study that tracked teenage males with or without ADHD into young adulthood found SUDs were 4 times more common among those with ADHD.⁹ Up to 45% of adults with ADHD have a history of alcohol abuse or dependence, and up to 30% have a history of illegal drug abuse or dependence.¹⁰

Conversely, an estimated 35% to 71% of alcohol abusers and 15% to 25% of substance-dependent patients have ADHD.¹¹ Adults with ADHD and comorbid SUD report earlier onset¹² and greater severity¹³ of substance abuse than adults without ADHD. Patients with ADHD experience earlier onset and higher rates of tobacco smoking by mid-adolescence.¹⁴

Developmental psychopathology. Longitudinal studies have suggested certain psychopathologic characteristics of ADHD can predispose an individual to SUDs independent of stimulant exposure. For example, inattention, impulsivity, and hyperactivity predispose an individual to develop an SUD and also are core symptoms of ADHD.¹⁵ Another study found impulsivity, impersistence, and difficulty sitting still at age 3 predicted alcohol abuse at age 21.¹⁶ A different longitudinal study found novelty-seeking behavior (restlessness, running/jumping and not keeping still, being squirmy and fidgety) between age 6 to 10 predicted adolescent drug abuse and cigarette smoking.¹⁷ Poor response inhibition is a key characteristic of ADHD and has been linked to adolescent drinking.¹⁸

ADHD may be an independent risk factor for SUD because a common neurobiologic psychopathology may predispose an individual to develop both conditions. The dopamine system has been implicated in SUD, and dysfunction in the dopaminergic circuits—mostly in basal and frontal cortex with consequent defects in executive function and reward system—also has been found in ADHD.¹⁹ Cognitive dysfunction associated with ADHD may decrease a patient’s ability to estimate the negative consequences of substance abuse and to delay immediate gratification from drug or alcohol use.

Clinical Point

A common neurobiologic psychopathology may predispose patients to develop ADHD and substance use disorders

ADHD patients are more vulnerable to SUDs if they have a comorbid condition, such as oppositional defiant disorder,^13,20 bipolar disorder,^20,21 or conduct disorder (CD).^20,22 Patients with ADHD and comorbid CD are estimated to be 8.8 times more likely to have an SUD before age 18 compared with those with ADHD alone.²³ Comorbid ADHD and CD may increase patients’ predisposition to develop dependence on highly addictive drugs, such as cocaine or methamphetamine.²⁴ Impaired executive function, behavioral dyscontrol, impulsivity, and peer rejection are common in both ADHD and CD and may increase the risk of developing SUDs in individuals who have both conditions.²⁵ Other risk factors for SUDs in patients with ADHD are listed in Table 1.²⁶

Table 1

Risk factors for SUDs in patients with ADHD

Presence of comorbid conditions (ie, oppositional defiant disorder, conduct disorder, bipolar disorder, eating disorder)
White or Hispanic race
Partially treated or residual ADHD symptoms
Attending a competitive college program
College youth who had late onset of stimulant treatment
Member of a college sorority/fraternity
ADHD: attention-deficit/hyperactivity disorder; SUDs: substance use disorders Source: Reference 26

Stimulants’ affect on SUD risk

Increased risk. Limited studies suggest exposure to stimulants is a risk factor for developing SUDs. In a longitudinal study, Lambert et al²⁷ followed 218 patients with ADHD and 182 without ADHD into adulthood and found a linear trend between duration of stimulant treatment and prevalence of cocaine dependence. ADHD patients exposed to stimulants for >1 year had the highest prevalence of cocaine abuse (27%), compared with untreated subjects (15%), or those treated with stimulants for <1 year (18%). However, the study did not control for comorbid contributing factors, such as CD.